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Role for VGLUT2 in selective vulnerability of midbrain dopamine neurons
by
Farino, Zachary J.
, Lu, Wei
, Freyberg, Zachary
, Hnasko, Thomas S.
, Steinkellner, Thomas
, Villeneuve, Michael
, Przedborski, Serge
, Zell, Vivien
, Sonders, Mark S.
, Freyberg, Robin J.
in
Basal ganglia
/ Biomedical research
/ Brain
/ Central nervous system diseases
/ Clonal deletion
/ Degeneration
/ Dopamine
/ Drosophila
/ Drosophila melanogaster
/ Gene expression
/ Genetic aspects
/ Glutamic acid transporter
/ Health aspects
/ Insects
/ Mesencephalon
/ Methamphetamine
/ Movement disorders
/ Neurodegenerative diseases
/ Neurons
/ Neurotoxins
/ Parkinson's disease
/ Physiology
/ Substantia nigra
/ Ventral tegmentum
2018
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Role for VGLUT2 in selective vulnerability of midbrain dopamine neurons
by
Farino, Zachary J.
, Lu, Wei
, Freyberg, Zachary
, Hnasko, Thomas S.
, Steinkellner, Thomas
, Villeneuve, Michael
, Przedborski, Serge
, Zell, Vivien
, Sonders, Mark S.
, Freyberg, Robin J.
in
Basal ganglia
/ Biomedical research
/ Brain
/ Central nervous system diseases
/ Clonal deletion
/ Degeneration
/ Dopamine
/ Drosophila
/ Drosophila melanogaster
/ Gene expression
/ Genetic aspects
/ Glutamic acid transporter
/ Health aspects
/ Insects
/ Mesencephalon
/ Methamphetamine
/ Movement disorders
/ Neurodegenerative diseases
/ Neurons
/ Neurotoxins
/ Parkinson's disease
/ Physiology
/ Substantia nigra
/ Ventral tegmentum
2018
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Do you wish to request the book?
Role for VGLUT2 in selective vulnerability of midbrain dopamine neurons
by
Farino, Zachary J.
, Lu, Wei
, Freyberg, Zachary
, Hnasko, Thomas S.
, Steinkellner, Thomas
, Villeneuve, Michael
, Przedborski, Serge
, Zell, Vivien
, Sonders, Mark S.
, Freyberg, Robin J.
in
Basal ganglia
/ Biomedical research
/ Brain
/ Central nervous system diseases
/ Clonal deletion
/ Degeneration
/ Dopamine
/ Drosophila
/ Drosophila melanogaster
/ Gene expression
/ Genetic aspects
/ Glutamic acid transporter
/ Health aspects
/ Insects
/ Mesencephalon
/ Methamphetamine
/ Movement disorders
/ Neurodegenerative diseases
/ Neurons
/ Neurotoxins
/ Parkinson's disease
/ Physiology
/ Substantia nigra
/ Ventral tegmentum
2018
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Role for VGLUT2 in selective vulnerability of midbrain dopamine neurons
Journal Article
Role for VGLUT2 in selective vulnerability of midbrain dopamine neurons
2018
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Overview
Parkinson's disease is characterized by the loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). DA neurons in the ventral tegmental area are more resistant to this degeneration than those in the SNc, though the mechanisms for selective resistance or vulnerability remain poorly understood. A key to elucidating these processes may lie within the subset of DA neurons that corelease glutamate and express the vesicular glutamate transporter VGLUT2. Here, we addressed the potential relationship between VGLUT expression and DA neuronal vulnerability by overexpressing VGLUT in DA neurons of flies and mice. In Drosophila, VGLUT overexpression led to loss of select DA neuron populations. Similarly, expression of VGLUT2 specifically in murine SNc DA neurons led to neuronal loss and Parkinsonian behaviors. Other neuronal cell types showed no such sensitivity, suggesting that DA neurons are distinctively vulnerable to VGLUT2 expression. Additionally, most DA neurons expressed VGLUT2 during development, and coexpression of VGLUT2 with DA markers increased following injury in the adult. Finally, conditional deletion of VGLUT2 made DA neurons more susceptible to Parkinsonian neurotoxins. These data suggest that the balance of VGLUT2 expression is a crucial determinant of DA neuron survival. Ultimately, manipulation of this VGLUT2-dependent process may represent an avenue for therapeutic development.
Publisher
American Society for Clinical Investigation
Subject
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